Oxytocin in schizophrenia: A review of evidence for its therapeutic effects

University of California, San Diego Medical Center Department of Psychiatry.
Acta Neuropsychiatrica (Impact Factor: 0.8). 06/2012; 24(3):130-146. DOI: 10.1111/j.1601-5215.2011.00634.x
Source: PubMed


MacDonald K, Feifel D. Oxytocin in schizophrenia: a review of evidence for its therapeutic effects.
Background: The suggestion that the neurohormone oxytocin may have clinical application in the treatment of schizophrenia was first published in 1972. Since then, a considerable body of research on a variety of fronts – including several recent double-blind treatment trials – has buttressed these early reports, providing support for the assertion that the oxytocin system is a promising and novel therapeutic target for this devastating malady. Herein, we review the diverse, convergent lines of evidence supporting the therapeutic potential of oxytocin in psychotic illness.
Methods: We performed a systematic review of preclinical and clinical literature pertaining to oxytocin's role in schizophrenia.
Results: Multiple lines of evidence converge to support the antipsychotic potential of oxytocin. These include several animal models of schizophrenia, pharmacological studies examining the impact of antipsychotics on the oxytocin system, human trials in patients examining the aspects of the oxytocin system and several double-blind, placebo-controlled clinical treatment trials.
Conclusions: There exists considerable, convergent evidence that oxytocin has potential as a novel antipsychotic with a unique mechanism of action. Auspiciously, based on the few chronic trials to date, its safety profile and tolerability appear very good. That said, several critical clinical questions await investigation before widespread use is clinically warranted.

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Available from: David Feifel, Mar 21, 2014
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    • "Functional imaging research has also shown that IN-OT increases brain activity in regions involved in social cognition (Bethlehem et al., 2013; Gordon et al., 2013) and modulates functional connectivity between these regions (Kirsch et al., 2005; Riem et al., 2013; Wittfoth-Schardt et al., 2012). Such research has led many to propose that IN-OT, through its effects on social behavior and cognition, may benefit a wide variety of psychiatric illnesses characterized by poor social functioning, such as ASDs (Modi and Young, 2012) and schizophrenia (MacDonald and Feifel, 2012). Reflecting the interest in OT's role in modulating social cognition and behavior, a search of PubMed using the terms " oxytocin " paired with " autism " , " anxiety " , and " schizophrenia " , demonstrates a steady increase in publications since the year 2000 (Fig. 1). "
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    ABSTRACT: Accumulating evidence demonstrates the important role of oxytocin (OT) in the modulation of social cognition and behavior. This has led many to suggest that the intranasal administration of OT may benefit psychiatric disorders characterized by social dysfunction, such as autism spectrum disorders and schizophrenia. Here, we review nasal anatomy and OT pathways to central and peripheral destinations, along with the impact of OT delivery to these destinations on social behavior and cognition. The primary goal of this review is to describe how these identified pathways may contribute to mechanisms of OT action on social cognition and behavior (that is, modulation of social information processing, anxiolytic effects, increases in approach-behaviors). We propose a two-level model involving three pathways to account for responses observed in both social cognition and behavior after intranasal OT administration and suggest avenues for future research to advance this research field.
    Neuroscience & Biobehavioral Reviews 12/2014; 49. DOI:10.1016/j.neubiorev.2014.12.011 · 8.80 Impact Factor
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    • "This makes OT a promising agent for conditions that are characterized by social anxiety or problems with the perception of social salience and reward (Bethlehem et al. 2013). An ameliorating effect of the neuropeptide on symptomatology and social cognitive impairments has been found in SZ (MacDonald & Feifel, 2012). "
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    ABSTRACT: Social neuroscience is a flourishing, interdisciplinary field that investigates the underlying biological processes of social cognition and behaviour. The recent application of social neuroscience to psychiatric research advances our understanding of various psychiatric illnesses that are characterized by impairments in social cognition and social functioning. In addition, the upcoming line of social neuroscience research provides new techniques to design and evaluate treatment interventions that are aimed at improving patients' social lives. This review provides a contemporary overview of social neuroscience in psychiatry. We draw together the major findings about the neural mechanisms of social cognitive processes directed at understanding others and social interactions in psychiatric illnesses and discuss their implications for future research and clinical practice.
    Psychological Medicine 10/2014; 45(06):1-21. DOI:10.1017/S0033291714002487 · 5.94 Impact Factor
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    • "This is the first study to demonstrate that non-peptide, systemically injected ligands for the OT receptor are capable of modifying light-induced circadian activity rhythms in a mammalian species. OT has been implicated as a potential therapeutic for the treatment of CNS disorders such as autism (Hollander et al., 2007), anxiety (Ring et al., 2006), depression (Kim et al., in press) and schizophrenia (MacDonald and Feifel, 2012). Dysfunction in circadian rhythms have been associated with each of these disorders and as such this study adds to the evidence warranting the study OT as a new potential therapeutic for CNS diseases of mood. "
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    ABSTRACT: The synchronization of circadian rhythms in sleep, endocrine and metabolic functions with the environmental light cycle is essential for health, and dysfunction of this synchrony is thought to play a part in the development of many neurological disorders. There is a demonstrable need to develop new therapeutics for the treatment of neurological disorders such as depression and schizophrenia, and oxytocin is currently being investigated for this purpose. There are no published reports describing activity of oxytocin receptor ligands on mammalian circadian rhythms and that, then, is the purpose of this study. Non-peptide oxytocin receptor ligands that cross the blood brain barrier were systemically injected in hamsters to determine their ability to modulate light-induced phase advances and delays of circadian wheel running rhythms. The oxytocin receptor agonist WAY267464 (10 mg/kg) inhibited light induced phase advances of wheel running rhythms by 55%, but had no effect on light-induced phase delays. In contrast, the oxytocin receptor antagonist WAY162720 (10 mg/kg) inhibited light-induced phase delays by nearly 75%, but had no effect on light-induced phase advances. Additionally, WAY162720 was able to antagonize the inhibitory effects of WAY267464 on light-induced phase advances. These results are consistent for a role of oxytocin in the phase-delaying effects of light on circadian activity rhythms early in the night. Therefore, oxytocin may prove to be useful in developing therapeutics for the treatment of mood disorders with a concomitant dysfunction in circadian rhythms. Investigators should also be cognizant that oxytocin ligands may negatively affect circadian rhythms during clinical trials for other conditions.
    Brain Research 10/2014; 1585. DOI:10.1016/j.brainres.2014.08.034 · 2.84 Impact Factor
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